AEG-1对大肠癌进展的影响

目的研究AEG-1在大肠癌组织和细胞中的表达,探讨AEG-1通过调控上皮间质转化和耐药参与大肠癌的进展。方法采用qRT-PCR检测AEG-1在大肠癌组织和细胞中的表达,统计AEG-1对大肠癌患者生存率的影响,分析其在不同癌症分期患者中的表达差异,并分析AEG-1表达量与大肠癌诊断敏感性的关系。采用体外实验将si-NC、pc-DNA-NC、si-AEG-1、pc-DNA-AEG-1转染到大肠癌SW116和LOVO细胞中,然后通过qRT-PCR检测转染效率以及AEG-1在两细胞系中的表达情况。采用CCK-8和克隆形成实验检测AEG-1对大肠癌细胞增殖的影响;采用流式细胞术检测转染后上皮间质转化和耐药情况的变化;采用Western blotting检测转染后上皮间质转化和耐药相关蛋白N-cadherin、E-cadherin、MRP的变化情况。结果 77例大肠癌患者组织中AEG-1表达水平明显高于对照组。浸润T3+T4期的患者中AEG-1的表达水平高于浸润T1+T2期患者。Ⅲ+Ⅳ期患者中AEG-1的表达水平高于Ⅰ+Ⅱ期。AEG-1高表达组患者OS时间明显低于低表达组。AEG-1表达量与大肠癌诊断敏感性之间呈显著正相关。在LOVO细胞系中,降低AEG-1表达后其细胞活力、侵袭力明显降低,同时间质细胞标志蛋白N-cadherin、上皮细胞标志蛋白E-cadherin、多药耐药相关蛋白MRP表达量降低。在SW116细胞系中,过表达AEG-1后上皮间质转化、耐药相关蛋白表达量显著升高。结论 AEG-1在大肠癌组织和细胞中的表达量明显上升,AEG-1通过调控上皮间质转化和耐药参与大肠癌的发生发展,为大肠癌的治疗提供了新的理论依据和新的靶点。

The impact of AEG-1 on colorectal cancer

Abstract: Objective To explore the expression of AEG-1 in colorectal cancer tissues and cells, and its role in the regulation of epithelial-mesenchymal transition and drug resistance in colorectal cancer. Methods The si-NC, pc-DNA-NC, si-AEG-1 and pc-DNA-AEG-1 were transfected into colorectal cancer cells SW116 and LOVO in vitro, and qRT-PCR was used to detect the transfection efficiency and expression of AEG-1 in the two cell lines of colorectal cancer. The differences in the expression of AEG-1 in different stages, and the relation between the expression of AEG-1 and the sensitivity of colorectal cancer diagnosis were analyzed. The impact of AEG-1 on the proliferation of colorectal cancer cells was detected with CCK-8 and clone formation assay. The impact of transfection on epithelial mesenchymal transformation and drug resistance was detected with flow cytometry. Western blotting was used to detect the changes in epithelial mesenchymal transition, drug resistance-related proteins N-cadherin, E-cadherin and MRP after transfection. Results The expression of AEG-1 in the 77 colorectal cancer patients was significantly higher than that in the 30 controls. The expression level of AEG-1 in patients with T3/T4 infiltration was higher than that in T1/T2 infiltration, and that in patients with stage III/IV was higher than that in stage I/II. The OS time in patients with high AEG-1 expression was significantly lower than that in patients with low expression. The expression of AEG-1 was positively related with the diagnostic sensitivity of colorectal cancer. In the LOVO cell line, the viability and invasion ability of downexpressed AEG-1 cells decreased significantly, and the expressions of interstitial cell marker protein N-cadherin, epithelial cell marker protein E-cadherin and multidrug resistance-associated protein MRP decreased. In the SW116 cell line, after overexpression of AEG-1, the expressions of epithelial-mesenchymal transition- and drug resistance-associated proteins increased significantly. Conclusion The expression of AEG-1 is obviously up-regulated in colorectal cancer tissues and cells. AEG-1 involves in the occurrence and development of colorectal cancer by regulating epithelial-mesenchymal transition. This result provides a new theoretical basis and new target for the treatment of colorectal cancer.